The Wilms tumor suppressor gene WT1, which is mutated in 10-15% of Wilms tumor -- a pediatric kidney cancer -- encodes a transcription factor with C2H2 zinc finger DNA binding domain. WT1 is proposed to regulate transcription of genes that are critical for the initiation and differentiation of kidney, gonad, spleen, and adrenal gland since wt1-null mouse embryos lack all of these organs. In addition to Wilms tumor, other human syndromes and diseases are also caused by mutations in the WT1 gene such as Danys-Drash and Frasier syndromes. In particular, Desmoplastic small round cell tumor (DSRCT) is a rare but extremely aggressive cancer arising in young adolescents in the abdominal area. In all cases of DSRCT examined to date, a novel fusion gene product between the Ewings Sarcoma gene (EWS) and the WT1 is created as a result of chromosomal translocation. Our laboratory is focused on understanding the functions of WT1 and EWS/WT1 gene products and how they are related to their respective cancer biology. Using microarray expression profiling, we have identified a number of WT1 target genes that appears to be important for kidney development. The target genes were independently verified using realtime-PCR, chromatin-immunoprecipitation, promoter-reporter assay and expression in WT1-positive cells in the develping kidneys. Identification of the target genes and defining their role during development will provide further insights to the development of Wilms tumor and organogenesis in general. As for the EWS/WT1 project, we are currently developing an animal model to better understand the etiology and the development of DSRCT and to develop possible therapeutics since there is no effective treatment for DSRCT.